What is the recommended initial dose of push-dose Levophed (norepinephrine) for an adult patient with severe hypotension or shock?

Push-Dose Norepinephrine Dosing

For push-dose norepinephrine in severe hypotension, prepare a 10 mcg/mL concentration by adding 1 mg (1 mL of 1 mg/mL) to 100 mL of normal saline, then administer 5-10 mL (50-100 mcg) as an IV bolus over 1-2 minutes, which can be repeated every 2-5 minutes as needed while preparing a continuous infusion. 1

Preparation Protocol

Standard Push-Dose Concentration

• Add 1 mg of norepinephrine to 100 mL of normal saline to create a 10 mcg/mL solution (1:100,000 concentration) 1
• This concentration allows for precise titration and reduces the risk of inadvertent overdosing 1

Alternative Concentration for Continuous Infusion

• The FDA-approved standard concentration is 4 mg norepinephrine in 1,000 mL of 5% dextrose (4 mcg/mL) 2
• Dextrose-containing solutions protect against oxidation and loss of potency; saline alone is not recommended for continuous infusions 2

Initial Bolus Dosing

Adult Dosing

• Initial bolus: 50-100 mcg (5-10 mL of 10 mcg/mL solution) IV push over 1-2 minutes 1
• Repeat every 2-5 minutes as needed for persistent hypotension 1
• Each bolus typically raises blood pressure for 5-10 minutes 1

Potency Considerations

• Norepinephrine is approximately 11 times more potent than phenylephrine 3
• 100 mcg of phenylephrine is roughly equivalent to 9 mcg of norepinephrine 3

Clinical Context for Push-Dose Use

Indications for Push-Dose Administration

• Profound hypotension with systolic BP ≤70 mmHg requiring immediate intervention 4
• Peri-intubation hypotension in critically ill patients 5
• Bridge therapy while preparing continuous vasopressor infusion 5
• Diastolic BP ≤40 mmHg or diastolic shock index (HR/DBP) ≥3 6

Critical Pre-Administration Requirements

• Address hypovolemia with crystalloid boluses (minimum 30 mL/kg) before or concurrent with norepinephrine 1, 7
• In severe hypotension (systolic <70 mmHg), start norepinephrine as an emergency measure while fluid resuscitation continues rather than waiting for complete volume repletion 1

Transition to Continuous Infusion

Starting Continuous Infusion

• Begin at 0.5 mg/h (approximately 8-12 mcg/min or 0.1-0.5 mcg/kg/min) 1, 2
• The FDA label recommends starting at 2-3 mL/min (8-12 mcg/min) of the 4 mcg/mL solution 2
• Titrate to achieve target MAP of 65 mmHg 1, 7

Titration Protocol

• Increase by 0.5 mg/h every 4 hours as needed, up to maximum of 3 mg/h 1
• Average maintenance dose ranges from 0.5-1 mL/min (2-4 mcg/min) of standard concentration 2
• Monitor blood pressure every 5-15 minutes during initial titration 1

Administration Route and Monitoring

Preferred Access

• Central venous access is strongly preferred to minimize extravasation risk 1, 4, 7
• If central access unavailable, peripheral IV can be used temporarily with strict monitoring 1
• Place arterial catheter as soon as practical for continuous blood pressure monitoring 1, 7

Extravasation Management

• If extravasation occurs, immediately infiltrate 5-10 mg phentolamine diluted in 10-15 mL saline into the site 1, 4, 2
• Pediatric phentolamine dose: 0.1-0.2 mg/kg up to 10 mg 1

Target Blood Pressure Goals

Standard Targets

• Target MAP ≥65 mmHg for most patients with septic shock 1, 7
• In previously hypertensive patients, raise BP no higher than 40 mmHg below pre-existing systolic pressure 2
• Patients with chronic hypertension may require MAP of 70-75 mmHg 7

Perfusion Markers Beyond MAP

• Monitor lactate clearance, urine output >50 mL/h, mental status, and capillary refill 1, 7
• Titrate to adequate tissue perfusion markers, not just blood pressure numbers 7

Special Considerations

Obesity

• Obese patients require lower weight-based doses (0.09 mcg/kg/min) compared to non-obese patients (0.13 mcg/kg/min) 8
• However, total non-weight-based doses are similar (approximately 8-9 mcg/min) 8
• Use actual body weight for initial dosing calculations in obese patients 8

Cardiac Considerations

• Use cautiously in patients with ischemic heart disease as it increases myocardial oxygen demand 4
• In septic shock specifically, norepinephrine may improve renal blood flow despite typically causing renal vasoconstriction 4

Common Pitfalls to Avoid

Critical Errors

• Never use norepinephrine in hypovolemic patients without concurrent fluid resuscitation 4, 6
• Do not mix with sodium bicarbonate or alkaline solutions in the IV line, as adrenergic agents are inactivated 1, 2
• Avoid abrupt withdrawal; reduce gradually when discontinuing 2
• Do not use solutions that are pinkish or darker than slightly yellow, or contain precipitate 2

Timing Considerations

• Early administration of norepinephrine (within first hour) may reduce mortality and fluid overload in profound hypotension 9, 6
• Duration and depth of hypotension strongly worsen outcomes; do not delay norepinephrine while waiting for complete fluid resuscitation in life-threatening hypotension 9, 6

Escalation for Refractory Hypotension

Second-Line Agents

• Add vasopressin 0.03 units/min when norepinephrine reaches 0.25 mcg/kg/min and hypotension persists 1, 7
• Consider epinephrine 0.1-0.5 mcg/kg/min as alternative second-line agent 1, 7
• Add dobutamine up to 20 mcg/kg/min for persistent hypoperfusion with myocardial dysfunction 1, 7

Agents to Avoid

• Do not use dopamine as first-line agent; associated with higher mortality and arrhythmias 4, 7
• Avoid phenylephrine except when norepinephrine causes serious arrhythmias or as salvage therapy 7
• Do not use low-dose dopamine for renal protection; no benefit and strongly discouraged 1, 7